l-Arginine transporters in cardiovascular disease: A novel therapeutic target

Chin-Dusting, J.P.F.; Willems, L.; Kaye, D.M.

doi:10.1016/j.pharmthera.2007.08.001

Cited by 69Nitric Oxide and Endothelin EffectsAmino Acid Enzymes and MetabolismRenin-Angiotensin System Studies

l-Arginine transporters in cardiovascular disease: A novel therapeutic target

Chin-Dusting, J.P.F., Willems, L., Kaye, D.M.·2007·Pharmacology & Therapeutics

DOI 10.1016/j.pharmthera.2007.08.001

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Abstract

The amino acid l-arginine participates in a variety of key biochemical and physiological activities, including its well-recognized role as the key substrate for nitric oxide (NO) biosynthesis. The current review describes the cellular influences on arginine metabolism with particular focus on the transport of l-arginine in the endothelium. It details the processes by which intracellular and extracellular levels of l-arginine may influence nitric oxide production and further documents the imbalance that is evident in various cardiovascular disease states. In man, impairment of l-arginine transport has been observed in hypertension, heart failure, and renal disease, and it may thus be a relevant therapeutic target for rectification of nitric oxide pathogenesis in these conditions.

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In recent years, it has become clear that extracellular l-arginine and ADMA concentrations, compartmentalization, and membrane transporters are important for NOS function.
“However, in recent years, it has become clear that extracellular l-arginine and ADMA concentrations, compartmentalization, and membrane transporters are important for NOS function, as will be discussed below in sect. IIIB4 (167, 668, 1030).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [167]
l-arginine import via the CAT1 transporter is critical for eNOS activity.
“Further studies showed that l-arginine import via the CAT1 transporter is critical for eNOS activity (167, 634).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [167]

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Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541 · see citing works
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Dysfunctional and Dysregulated Nitric Oxide Synthases in Cardiovascular Disease: Mechanisms and Therapeutic Potential
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The Role of Asymmetric Dimethylarginine and Arginine in the Failing Heart and Its Vasculature
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Impact of Arginine Nutrition and Metabolism during Pregnancy on Offspring Outcomes
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Serum asymmetric dimethylarginine and arginine levels predict microvascular and macrovascular complications in type 2 diabetes mellitus
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Resveratrol inhibits lipid accumulation in the intestine of atherosclerotic mice and macrophages
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A novel biodegradable and biologically functional arginine-based poly(ester urea urethane) coating for Mg–Zn–Y–Nd alloy: enhancement in corrosion resistance and biocompatibility
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Ruscogenin Alleviates Myocardial Ischemia-Induced Ferroptosis through the Activation of BCAT1/BCAT2
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Calcium-activated potassium channels – a therapeutic target for modulating nitric oxide in cardiovascular disease?
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Arginine-leucine based poly (ester urea urethane) coating for Mg-Zn-Y-Nd alloy in cardiovascular stent applications
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Insulin requires A1 adenosine receptors expression to reverse gestational diabetes-increased L-arginine transport in human umbilical vein endothelium
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The circulating level of miR-122 is a potential risk factor for endothelial dysfunction in young patients with essential hypertension
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New approaches to the design and discovery of therapies to prevent erectile dysfunction
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Say NO to Obesity-Related Hypertension
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Augmented endothelial‐specific L ‐arginine transport prevents obesity‐induced hypertension
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Impaired l -arginine-nitric oxide pathway contributes to the pathogenesis of resistant hypertension
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Combined effects of aerobic exercise and l -arginine ingestion on blood pressure in normotensive postmenopausal women: A crossover study
Puga, G. M., Novais, I. D. P., Katsanos, C. S., & Zanesco, A. (2016) · Life Sciences · doi:10.1016/j.lfs.2016.02.091 · Cited by 29 · see citing works
Reduced L ‐arginine transport contributes to the pathogenesis of myocardial ischemia‐reperfusion injury
Venardos, K. M., Zatta, A. J., Marshall, T., Ritchie, R. H., & Kaye, D. M. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22235 · Cited by 25 · see citing works
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Alterations in l-arginine and inflammatory markers in type 2 diabetic patients with and without microalbuminuria
Barış, N., Erdoğan, M., Sezer, E., Saygılı, F., Ozgonul, A. M., Turgan, N., & Ersöz, B. (2009) · Acta Diabetologica · doi:10.1007/s00592-008-0089-9 · Cited by 25 · see citing works
Serum adenosine deaminase activity and coronary artery disease: a retrospective case-control study based on 9929 participants
Xuan, C., Tian, Q., Zhang, S., Li, H., Tian, T., Zhao, P., Yue, K., Ling, Y., He, G., & Lun, L. (2019) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622319891539 · Cited by 22 · see citing works
The Endothelium, Part II: EDHF-Mediated Responses "The Classical Pathway"
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Endothelial-transcytosed myeloperoxidase activates endothelial nitric oxide synthase via a phospholipase C-dependent calcium signaling pathway
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Obesity‐Induced Hypertension: Heavy on the Accelerator
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Effect of chronic nitrate and citrulline supplementation on vascular function and exercise performance in older individuals
Roux‐Mallouf, T. L., Pelen, F., Vallejo, A., Halimaoui, I., Doutreleau, S., & Vergès, S. (2019) · Aging · doi:10.18632/aging.101984 · Cited by 18 · see citing works
The Physiological Effects of Amino Acids Arginine and Citrulline: Is There a Basis for Development of a Beverage to Promote Endurance Performance? A Narrative Review of Orally Administered Supplements
Speer, H., D'Cunha, N. M., Davies, M. J., McKune, A. J., & Naumovski, N. (2020) · Beverages · doi:10.3390/beverages6010011 · Cited by 18 · see citing works
Gasotransmitters for the Therapeutic Prevention of Hypertension and Kidney Disease
Hsu, C., & Tain, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22157808 · Cited by 18 · see citing works
Endothelial calcium-activated potassium channels as therapeutic targets to enhance availability of nitric oxide
Kerr, P. M., Tam, R., Narang, D., Potts, K. G., McMillan, D., McMillan, K., & Plane, F. (2012) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y2012-075 · Cited by 18 · see citing works
L-Arginine Transport and Nitric Oxide Synthesis in Human Endothelial Progenitor Cells
Díaz-Pérez, F., Radojkovic, C., Aguilera, V., Veas, C., González, M., Lamperti, L., Escudero, C., & Aguayo, C. R. (2012) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e318269ae2f · Cited by 17 · see citing works
Effects of acute nitric oxide precursor intake on peripheral and central fatigue during knee extensions in healthy men
Roux‐Mallouf, T. L., Laurent, J., Besset, D., Marillier, M., Larribaut, J., Belaïdi, E., Corne, C., Doutreleau, S., & Vergès, S. (2019) · Experimental Physiology · doi:10.1113/ep087493 · Cited by 17 · see citing works
Endothelial cationic amino acid transporter-1 overexpression can prevent oxidative stress and increases in arterial pressure in response to superoxide dismutase inhibition in mice
Konstantinidis, G., Head, G. A., Evans, R. G., Nguyen‐Huu, T., Venardos, K. M., Croft, K. D., Mori, T. A., Kaye, D. M., & Rajapakse, N. W. (2014) · Acta Physiologica · doi:10.1111/apha.12215 · Cited by 16 · see citing works
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Exploring the Biotechnological Value of Marine Invertebrates: A Closer Look at the Biochemical and Antioxidant Properties of Sabella spallanzanii and Microcosmus squamiger
Pan, Y.-L., Rodrigues, M. J., Pereira, C. G., Engrola, S. A. D., Colen, R., Mansinhos, I., Romano, A., Andrade, P. B., Fernandes, F., & Custódio, L. M. B. (2021) · Animals · doi:10.3390/ani11123557 · Cited by 14 · see citing works
Cardio-protective effects of combined l-arginine and insulin: Mechanism and therapeutic actions in myocardial ischemia-reperfusion injury
Venardos, K. M., Rajapakse, N. W., Williams, D., Hoe, L. E. S., Peart, J. N., & Kaye, D. M. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.10.046 · Cited by 12 · see citing works
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Contribution of SLC7A1 genetic variant to hypertension, the TAMRISK study
Määttä, K. M., Kunnas, T. A., & Nikkari, S. T. (2013) · BMC Medical Genetics · doi:10.1186/1471-2350-14-69 · Cited by 8 · see citing works
Serum adenosine deaminase activity and acute cerebral infarction: a retrospective case-control study based on 7913 participants
Ling, Y., Jiang, C., Xiao, Z., Shang, X., Li, Q., Wang, B., Hao, M., Liu, F., Zhao, N., Feng, J., et al. (2022) · Aging · doi:10.18632/aging.204338 · Cited by 7 · see citing works
Medicinal Chemistry and Therapeutic Applications of the Gasotransmitters NO , CO , and H 2 S and their Prodrugs
Szabó, C. (2010) · Wiley eBooks · doi:10.1002/0471266949.bmc178 · Cited by 7 · see citing works
L-Arginine Supplementation Mitigates Dichlorvos-Induced Haematocardiotoxicity, and Oxidative Stress in Male Wistar Rats
Saka, W. A., Igbayilola, Y. D., Jabba, H. L., Muftaudeen, T. K., Adejumo, R., Alu, T. D., Ikuomola, M., Ojelere, J. T., & Adegoke, V. O. (2024) · Open Journal of Applied Sciences · doi:10.4236/ojapps.2024.147123 · Cited by 6 · see citing works
Augmented endothelial l ‐arginine transport ameliorates pressure‐overload‐induced cardiac hypertrophy
Rajapakse, N. W., Johnston, T., Kiriazis, H., Chin-Dusting, J. P. F., Du, X., & Kaye, D. M. (2015) · Experimental Physiology · doi:10.1113/ep085250 · Cited by 6 · see citing works
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Effects of Dietary l-Arginine on Nitric Oxide Bioavailability in Obese Normotensive and Obese Hypertensive Subjects
Giam, B., Kuruppu, S., Head, G. A., Kaye, D. M., & Rajapakse, N. W. (2016) · Nutrients · doi:10.3390/nu8060364 · Cited by 6 · see citing works
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L-cysteine/d,L-homocysteine-regulated ileum motility via system L and B°,+ transporter: Modification by inhibitors of hydrogen sulfide synthesis and dietary treatments
Yamane, S., Nomura, R., Yanagihara, M., Nakamura, H., Fujino, H., Matsumoto, K., Horie, S., & Murayama, T. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.07.042 · Cited by 6 · see citing works
Cardiovascular disease: primary prevention, disease modulation and regenerative therapy
Sultan, S., & Hynes, N. (2012) · Vascular · doi:10.1258/vasc.2012.ra0062 · Cited by 5 · see citing works
CAT1 silencing inhibits TGF-β1-induced mouse hepatic stellate cell activation in vitro and hepatic fibrosis in vivo
Peng, F., Tian, Y., Ma, J., Xu, Z., Wang, S., Tang, M., Lei, J., Gong, G., & Jiang, Y. (2020) · Cytokine · doi:10.1016/j.cyto.2020.155288 · Cited by 5 · see citing works
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L-Arginine transporters in cardiovascular disease: a novel theraputic target
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Authors: Chin-Dusting, J. P. F., Willems, L., & Kaye, D. M.
Affiliations: The Alfred Hospital (AU)
Corresponding author: Willems, L.
ORCID: Willems, L.
Kaye, D.M.
Venue: Pharmacology & Therapeutics
Publisher: Elsevier BV
Published: 2007-12
Volume: 116
Issue: 3
Pages: 428-436
ISSN: 0163-7258 (ISSN-L)
DOI: 10.1016/j.pharmthera.2007.08.001
OpenAlex: W2023387731
Cited by: 69
References: 119
Citations by year: 2026: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 8 · 2018: 1 · 2017: 3 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 6 · 2012: 6
FWCI: 0.29
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Keywords: arginine transport, nitric oxide production, endothelium, arginine metabolism, cardiovascular disease, hypertension, heart failure, kidney disease, therapeutic target
MeSH terms: Animals, Arginine, Biological Transport, Cardiovascular Diseases, Humans, Kinetics, Nitric Oxide, Amino Acid Transport Systems, Basic

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l-Arginine transporters in cardiovascular disease: A novel therapeutic target

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